促肾上腺皮质激素的中枢抗阿片镇痛效应及其作用机制分析

Adrenocorticotropic Hormone(ACTH):Antagonistic Effect on Opioid Analgesia in Central Nervous System of the Rat and Its Possible Mechanisms of Action

本研究采用多种方法在行为学、细胞受体、受体后第二信使以及脑内Ｆｏｓ蛋白的诱导表达等多个水平，对ＡＣＴＨ的中枢抗阿片镇痛效应、作用机制以及作用部位进行了深入的观察。结果表明，ＡＣＴＨ在脊髓水平可以对抗阿片μ和δ受体介导的镇痛，不对抗κ受体所介导的镇痛。进一步研究表明，ＡＣＴＨ的这一效应可能不是直接发生在阿片受体上的对抗，而是在受体后ｃＡＭＰ和Ｃａ（２＋）信使通路上与阿片相互作用的结果。另外，ＡＣＴＨ可以诱导脑内许多核团中Ｆｏｓ蛋白的表达，其中包括与痛觉调制有关的核团，推测ＡＣＴＨ可能通过激活这些核团的神经元发挥其中枢效应。

Using the behavioral pharmacological approach,we have studied the influence of ACTH on the analgesia mediated by three types of opioid receptors(μ,δ,κ). The mechanisms by which ACTH antagonizes opioid analgesia were explored at receptor level and post-receptor second messenger level. The expression of Fos protein induced by ACTH was also observed in rat brain. The main results show that ACTH selectively antagonlzes spinal opioid analgesia mediated by μ and δ, but not κ receptors. The proposed mechanisms of the anti-opioid effect of ACTH are that ACTH can modulate opioid-induced decrease of intracellular cAMP content and the suppression of calcium influx. ACTH has been shown to induce Fos protein expression in selected brain areas including the nuclei involved in pain modulation.These brain areas may serve as sites of action for ACTH to exert its anti-opioid effect.